Significant levels of TNF (578 +/- 917 pg/ml versus 24 +/- 29 pg/ml) (p = 0.01), GM-CSF (24 +/- 41 pg/ml versus less than 8 pg/ml) (p = 0.02), and IL-6 (225 +/- 327 pg/ml versus 7 +/- 12 pg/ml) (p = 0.01), but not IL-1 alpha or IL-4, were detected in the bronchoalveolar lavage fluid (BALF) of patients with symptomatic compared with BALF of patients with asymptomatic asthma.
Glucocorticoids activated the glucocorticoid receptor and inhibited serum-induced secretion of interleukin-6 in bronchial smooth-muscle cells from both subjects with asthma and those without asthma; however, glucocorticoids inhibited proliferation only in bronchial smooth-muscle cells from subjects without asthma.
Among individuals with both asthma/atopy and the IL-6 -634 G allele, however, risk was increased at least 3-fold (OR = 3.1, 95% CI = 1.2-8.3 for all cancers and OR = 4.2, 95% CI = 1.5-11.6 for adenocarcinomas) relative to individuals with no asthma/atopy and the CC genotype.
Cases showed significant higher frequency of the genotypes: IL-6-174 GG (P<0.05, OR=3.2, 95% CI=1.09-10) that was evident mainly in the uncontrolled asthma subgroup indicative of the possibility of being a severity genotype.
Cases showed significant higher frequency of the genotypes: IL-6-174 GG (P<0.05, OR=3.2, 95% CI=1.09-10) that was evident mainly in the uncontrolled asthma subgroup indicative of the possibility of being a severity genotype.
Alterations in the expression of Stat3, Socs3 and IL-6 were determined in a murine model of asthma, where Balb/c mice were sensitized and challenged with OVA (OVA/OVA) and compared with control mice sensitized and challenged with saline (SAL) (SAL/SAL) mice.
The allele and genotype frequencies of a number polymorphic genes coding for tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 alpha, IL-1 beta, IL-1 receptor (IL-1R), IL-1RA, and IL-6 were investigated in 60 patients with asthma in comparison with 140 controls using polymerase chain reaction with sequence-specific primers.
Four functional IL6 single nucleotide polymorphisms (SNPs) and a nonsynonymous IL6R SNP were genotyped in 700 Mexican and Puerto Rican asthma families and in 443 African-American asthma cases and controls.
In the BAL fluid, IL-13 and IL-6 differentiated subjects with asthma from controls, whereas growth-related oncogene (CXCL1), RANTES (CCL5), IL-12, IFN-gamma, and IL-10 best characterized severe versus moderate asthma in children.
We used recombinant sgp130Fc protein and recently generated transgenic mice expressing high levels of sgp130Fc to discriminate between classic and trans-signaling in vivo, and demonstrated that IL-6 trans-signaling is critically involved in generation and maintenance of several inflammatory and autoimmune diseases including chronic inflammatory bowel disease, rheumatoid arthritis, peritonitis and asthma, as well as inflammation-induced colon cancer.
However, recent studies support a dissociation of IL-6 from inflammation in the lung and suggest that this cytokine plays an active role in pathogenesis of asthma and, in all likelihood, COPD.
Dexamethasone's trans-activation of GILZ and trans-repression of NF-kB-driven IL-6 expression were both inhibited by IL2 + 4; IL17 + IL23 antagonized Dex trans-repression in PBMC from asthmatics.
Although a common, non-synonymous variant in the IL-6 receptor gene (IL6R rs2228145" genes_norm="3570">Asp358Ala; rs2228145 A>C) is associated with the risk of several common diseases, with the 358Ala allele conferring protection from coronary heart disease (CHD), rheumatoid arthritis (RA), atrial fibrillation (AF), abdominal aortic aneurysm (AAA), and increased susceptibility to asthma, the variant's effect on IL-6 signaling is not known.
Subjects with an elevation of both hsCRP and IL-6 were grouped as asthmatics with systemic inflammation, and those with both hsCRP and IL-6 within the normal ranges were grouped as asthmatics without systemic inflammation.
Asthmatics with glutathione S-transferase P1 Val(105)/Val(105) compared with asthmatics with the glutathione S-transferase P1 Val(105)/Ile(105) and Ile(105)/Ile(105) had greater generation of acute phase cytokines (TNF-α, IL-6, CXCL8), IL-12, CCL11, thromboxane B2 and immunoglobulin E at 24 h after local allergen challenge.
The airway epithelium is a major contributor to asthma pathology and has been shown to produce an excess of inflammatory and pro-remodelling cytokines such as TGF-β, IL-6 and IL-8 as well as deficient amounts of anti-viral interferons.
ASM from patients with severe asthma shows greater proliferation and IL-6 release than in patients with nonsevere asthma, but both groups show corticosteroid insensitivity. miR-221 regulates p21(WAF1) and p27(kip1) expression levels.
In conclusion, our studies led to identification of some key candidate genes, namely IRF2, IL6, IFNGR2, STAT4 and IL4RA that modulate genetic susceptibility to asthma in the Indian population.